Comparison of Beta-value and M-value methods for quantifying methylation levels by microarray analysis.

Published online

Journal Article

BACKGROUND: High-throughput profiling of DNA methylation status of CpG islands is crucial to understand the epigenetic regulation of genes. The microarray-based Infinium methylation assay by Illumina is one platform for low-cost high-throughput methylation profiling. Both Beta-value and M-value statistics have been used as metrics to measure methylation levels. However, there are no detailed studies of their relations and their strengths and limitations. RESULTS: We demonstrate that the relationship between the Beta-value and M-value methods is a Logit transformation, and show that the Beta-value method has severe heteroscedasticity for highly methylated or unmethylated CpG sites. In order to evaluate the performance of the Beta-value and M-value methods for identifying differentially methylated CpG sites, we designed a methylation titration experiment. The evaluation results show that the M-value method provides much better performance in terms of Detection Rate (DR) and True Positive Rate (TPR) for both highly methylated and unmethylated CpG sites. Imposing a minimum threshold of difference can improve the performance of the M-value method but not the Beta-value method. We also provide guidance for how to select the threshold of methylation differences. CONCLUSIONS: The Beta-value has a more intuitive biological interpretation, but the M-value is more statistically valid for the differential analysis of methylation levels. Therefore, we recommend using the M-value method for conducting differential methylation analysis and including the Beta-value statistics when reporting the results to investigators.

Full Text

Duke Authors

Cited Authors

  • Du, P; Zhang, X; Huang, C-C; Jafari, N; Kibbe, WA; Hou, L; Lin, SM

Published Date

  • November 30, 2010

Published In

Volume / Issue

  • 11 /

Start / End Page

  • 587 -

PubMed ID

  • 21118553

Pubmed Central ID

  • 21118553

Electronic International Standard Serial Number (EISSN)

  • 1471-2105

Digital Object Identifier (DOI)

  • 10.1186/1471-2105-11-587

Language

  • eng

Conference Location

  • England